Characterization and assessment of the potential toxicity/pathogenicity of fibrous glaucophane.

In California, the metamorphic blueschist occurrences within the Franciscan Complex are commonly composed of glaucophane, which can be found with a fibrous habit. Fibrous glaucophane's potential toxicity/pathogenicity has never been determined and it has not been considered by the International Agency for Research on Cancer (IARC) as a potential carcinogen to date. Notwithstanding, outcrops hosting fibrous glaucophane are being excavated today in California for building/construction purposes (see for example the Calaveras Dam Replacement Project - CDRP).

Bile salt-coating modulates the macrophage uptake of nanocores constituted by a zidovudine prodrug and enhances its nose-to-brain delivery.

We have previously demonstrated that the ester conjugation of zidovudine (AZT) with ursodeoxycholic acid (UDCA) allows to obtain a prodrug (U-AZT) which eludes the active efflux transporters (AET). This allows the prodrug to more efficiently permeates and remains in murine macrophages than the parent compound. Here we demonstrate that U-AZT can be formulated, by a nanoprecipitation method, as nanoparticle cores coated by bile acid salt (taurocholate or ursodeoxycholate) corona, without any other excipients.

Conveying a newly designed hydrophilic anti-human thymidylate synthase peptide to cisplatin resistant cancer cells: are pH-sensitive liposomes more effective than conventional ones?

Context: LR-peptide, a novel hydrophilic peptide synthetized and characterized in previous work, is able to reduce the multi-drug resistance response in cisplatin (cDPP) resistant cancer cells by inhibiting human thymidylate synthase (hTS) overexpressed in several tumors, including ovarian and colon-rectal cancers, but it is unable to enter the cells spontaneously.

Objective: The aim of this work was to design and characterize liposomal vesicles as drug delivery systems for the LR peptide, evaluating the possible benefits of the pH-responsive feature in improving intracellular delivery.

Materials And Methods: For this purpose, conventional and pH-sensitive liposomes were formulated, compared regarding their physical-chemical properties (size, PDI, morphology, in vitro stability and drug release) and studied for in vitro cytotoxicity against a cDDP-resistant cancer cells.

Enhanced anti-hyperproliferative activity of human thymidylate synthase inhibitor peptide by solid lipid nanoparticle delivery.

Recently, octapeptide LSCQLYQR (LRp), reducing growth of cis-platinum (cDDP) resistant ovarian carcinoma cells by inhibiting the monomer-monomer interface of the human enzyme thymidylate synthase, has been identified. As the peptide is not able to cross the cell membrane it requires an appropriate delivery system. In this work the application of SLNs, biocompatible and efficient tools for the intracellular drug transport, applied especially for lipophilic drugs, was exploited for the delivery of the hydrophilic peptide LRp.

The zeta potential of mineral fibres.

For the first time, the zeta (ξ) potential of pathogenic mineral fibres (chrysotiles, amphiboles and erionite) was systematically investigated to shed light on the relationship between surface reactivity and fibre pathogenicity. A general model explaining the zeta potential of chrysotile, amphiboles and erionite has been postulated. In double distilled water, chrysotiles showed positive values while crocidolite and erionite showed negative values.

Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid.

Context: Zidovudine (AZT) is employed against AIDS and hepatitis; its use is limited by active efflux transporters (AETs) that induce multidrug resistance for intracellular therapies and hamper AZT to reach the brain. Ursodeoxycholic acid (UDCA) conjugation with AZT (prodrug UDCA-AZT) allows to elude the AET systems.

Objective: To investigate the effect of the Pluronic F68 coating on the loading, release and stability of poly(D,L lactide-co-glicolide) nanoparticles (NPs) embedded with UDCA-AZT.

Design flexibility influencing the in vitro behavior of cationic SLN as a nonviral gene vector.

Several advanced in vitro and in vivo studies have proved the broad potential of cationic solid lipid nanoparticles (SLN) as nonviral vectors. However, a few data are available about the correlation between lipid component of the SLN structure and in vitro performance in terms of cell tolerance and transfection efficiency on different cell lines. In this paper SLN were prepared using stearic acid as main lipid component, stearylamine as cationic agent and protamine as transfection promoter and adding phosphatidylcholine (PC), cholesterol (Chol) or both to obtain three different multicomponent SLN (SLN-PC, SLN-Chol and SLN-PC-Chol, respectively).

Structural investigation and intracellular trafficking of a novel multicomposite cationic solid lipid nanoparticle platform as a pDNA carrier.

Background: The ability to efficiently cross cellular barriers and accomplish high-level transgene expression is a critical challenge to broad application of nonviral vectors, such as cationic solid lipid nanoparticles (SLN).

Aims: This study aims to design and characterize in vitro multicomposite SLN as a novel platform for pDNA delivery.

Results/discussion: The distribution of each component (stearic acid, stearylamine, phosphatidylcholine, cholesterol, protamine and Pluronic F68) in the SLN matrix was studied by electron spectroscopy for chemical analysis and NMR in order to establish its influence on SLN cytotoxicity and transfection efficiency.